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European cholesterol guidelines push LDL targets below 55 mg/dL

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A welcome addition for managing lipid disorders
Paul S. Jellinger, MD

The new ESC dyslipidemia guidelines recently presented at the society’s annual congress are a welcome addition to the lipid disorder treatment guidelines available to clinicians. These guidelines follow the groundbreaking recommendation in 2017 by AACE in their updated guidelines that introduced an LDL goal of <55 mg/dL in “extreme risk” patients. The ESC guidelines now also recommend an LDL goal of <55 mg/dL in “very-high-risk” patients but go further by also requiring a 50% reduction in LDL. Furthermore, they have established an LDL goal of <40 mg/dL in patients who experienced a second vascular event in the past 2 years while on maximally tolerated statin dose.

The ESC very-high-risk category shares many features with AACE’s extreme-risk category but is broader in that it includes patients without a clinical event who display unequivocal evidence of arteriosclerotic cardiovascular disease (ASCVD) on imaging and patients with severe chronic kidney disease (GFR <30 mL/min ) without known ASCVD. There are substantial differences between the ESC and AHA-ACC 2018 guidelines in the very-high-risk category. The AHA very-high-risk is directed toward secondary prevention only and requires two major ASCVD events or one major and at least two high-risk conditions. Moreover, elements of both major ASCVD events and high-risk conditions as well as the very-high-risk eligibility requirements could mean that some patients, who would clearly be classified by both ESC and AACE as candidates for an LDL goal of <55, may not qualify for threshold consideration for maximal LDL lowering below 70 mg/dL including the use of PCSK9 inhibitors. Relative to this point, the AHA-ACC guidelines do not classify past CABG or PCI as a major ASCVD event, nor is a TIA considered a major event or a high-risk condition.

For LDL, “lower is better” is supported by years of statin clinical trial evidence, along with the robust findings in the 2010 Cholesterol Trialists Collaboration. The goal of <55 mg/dL is supported by the IMPROVE-IT, FOURIER, and ODYSSEY trials. The ESC guidelines appropriately take this body of evidence and applies it to an aggressive treatment platform that, like AACE, sets clinically useful LDL goals for clinicians and patients. It takes early, aggressive LDL-lowering treatment to stay ahead of atherosclerotic plaque development in patients who are at very high or extreme risk. Following AACE’s lead, the ESC guidelines are the newest tool available to clinicians addressing this issue with the promise of further decreasing CVD events and extending lives.

Dr. Jellinger is a member of the editorial advisory board for Clinical Endocrinology News. He is professor of clinical medicine on the voluntary faculty at the University of Miami Miller School of Medicine and a practicing endocrinologist at The Center for Diabetes & Endocrine Care in Hollywood, Fla. He is past president of the American Association of Clinical Endocrinologists and the American College of Endocrinology and was chair of the writing committee for the 2017 AACE-ACE lipid guidelines.



However, other experts see an important difference in the risk faced by patients who reach the ESC’s recommended treatment goals and those who fall just short.

“It’s hard to lower an LDL-cholesterol that is already relatively low. People who are close to their cholesterol target need the most intensified treatment” to reach their goal, said Rory Collins, F.Med.Sci., professor of epidemiology at Oxford University. He was not on the ESC guidelines panel.

Dr. Rory Collins, Oxford (England) University

Dr. Rory Collins

“It’s a mind shift that clinicians need to be most aggressive in treating patients with the highest risk” even when their LDL-cholesterol is low but not yet at the target level, Dr. Collins said during a discussion session at the congress.

The new ESC guidelines is about “both getting the LDL-cholesterol down to a certain level and also about achieving a big [at least 50%] change” from baseline. “I think the ESC guidelines make that crystal clear,” said Marc S. Sabatine, MD, professor of medicine at Harvard Medical School, Boston, and the sole American to participate in the ESC guidelines-writing panel.

Dr. Marc S. Sabatine, professor of medicine, Harvard Medical School, Boston Mitchel L. Zoler/MDedge News

Dr. Marc S. Sabatine

The ESC also broke new ground by advocating an aggressive path toward achieving these LDL-cholesterol goals by elevating the newest and most potent class of approved LDL-cholesterol-lowering drugs, the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors, to a top-tier, class I recommendation (“is recommended”) for secondary prevention in very-high-risk patients not reaching their goal LDL-cholesterol level on a maximally tolerated statin plus ezetimibe. This recommendation to unequivocally add a PCSK9 inhibitor for this patient population contrasts with the 2018 AHA/ACC guideline that deemed adding a PCSK9 inhibitor a IIa recommendation (“is reasonable”).

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